Epithelial polarity, or the coordinated orientation of cells within an epithelium, is critical for the development and function of the vertebrate retina. The vertebrate retina develops from an undifferentiated neuroepithelium into an organized and laminated structure that demonstrates a high degree of polarity at both the tissue and cellular levels. A long-term goal of this project is to understand the molecular and cellular mechanisms that regulate the establishment of epithelial polarity. Accumulating evidence suggests these mechanisms are conserved between flies and vertebrates. This proposal uses the Drosophila retina as a model system to study this poorly understood process. The powerful molecular and genetic tools available in Drosophila and the exceptional accessibility of the retina to genetic screens make the Drosophila retina an ideal system in which to study this process. An understanding of the mechanisms that govern the establishment of epithelial polarity is essential for the development of therapeutic strategies for retinal disease, particularly those that target congenital defects. This work focuses on strabimus (stbm), a novel tissue polarity gene in Drosophila with a highly conserved vertebrate homolog. A specific aim of this work is to understand the role of Stbm in this process by carrying out a structure/function analysis of the protein. A second specific aim of this work is to use genetic and biochemical screens to identify genes and proteins that interact with stbm to orient cells in a coordinated fashion in epithelia.